Osteoporosis

Preface to the Fourth Edition

Contributors

Editor’s Note

Part I: Introduction

Chapter 1. The Bone Organ System: Form and Function

Introduction

Composition and Organization of Bone

Cellular Components of Bone

Bone Homeostasis

Basic Bone Mechanics

Summary

References

Chapter 2. The Nature of Osteoporosis

Defining Osteoporosis

Material and Structural Basis of Skeletal Fragility

Summary

References

Chapter 3. Reflections on Osteoporosis

Introduction

Definition

Diagnosis

Fragility Fractures

Bone Density and Fracture Risk

Pathogenesis

Prevention

Treatment

Summary

References

Chapter 4. Reflections on Development of Concepts of Intercellular Communication in Bone

Introduction

Calcium Homeostasis – Developments of the 1960s

Discovery of Calcitonin

Inhibition of Bone Resorption by Calcitonin

Lessons from an Osteogenic Sarcoma

Emergence of Bone Cell Biology

Could Osteoblasts Regulate Osteoclasts?

The Origin of Osteoclasts – Mid-1970s

Osteoblast Regulation of Osteoclasts

Control of Osteoclast Formation

Hormone and Cytokine Control of Osteoclast Formation

The Physiologic Signaling Mechanisms in Osteoclast Control

Bone Remodeling

Coupling of Bone Formation to Resorption

Coupling Factor – from Matrix or Cells?

Communication from Osteocytes

Is There a Single “Coupling Factor”, Analogous to RANKL?

PTHrP as a Local Control Process

How Might PTHrP Participate?

Summary

Acknowledgments

References

Chapter 5. Osteo-Odyssey: A Memoir

Starting Out: From A to B One

Being the First Postdoc in Larry’s Lab

In the Academic World: Projects and People

The Bone World Beyond the Laboratory: ASBMR and NOF

References

Part II: Cellular, Molecular, and Developmental Biology of Bone

Chapter 6. Development of the Skeleton

Overview

Patterning the Skeleton

Endochondral Bone Formation

Signaling Pathways that Regulate Endochondral Bone Formation

Intramembranous Bone Formation

References

Chapter 7. The Skeletal Stem Cell

Introduction

Defining Skeletal Stem Cells

Migration of Skeletal Stem Cells

Kinetics of Skeletal Cell Turnover

Potential Use of Skeletal Stem Cells as Therapy

Interactions with the Hematopoietic System

Summary

References

Chapter 8. Osteoclast Biology

Introduction

Osteoclast Formation

Osteoclast Function

Conclusions

Acknowledgments

References

Chapter 9. Osteoblast Biology

Overview

Phenotypic Properties of Osteogenic Lineage Cells

Developmental Sequence of Osteoblast Phenotype Development

Markers of Osteoblast Maturation Stages

Genetic and Epigenetic Control of Gene Expression Regulating Skeletal Biology and Pathology

Concluding Remarks

Acknowledgments

References

Chapter 10. Osteocyte Biology

Introduction

Osteocyte Ontogeny

Osteoid-Osteocytes

Osteocyte Selective Genes/Proteins and Their Potential Functions

Morphology of Osteocytes: Lacunocanalicular System and Dendrite Formation

Osteocyte Cell Models

Mechanisms and Response of Osteocytes to Mechanical Forces

Osteocyte Signals for Bone Formation

Osteocyte Signals for Bone Resorption

Osteocyte Apoptosis and Autophagy

Osteocyte Modification of Their Microenvironment

Osteocyte Regulation of Phosphate Metabolism

Role of Gap Junctions and Hemichannels in Osteocyte Communication

Osteocytes in the Embryonic and the Adult Skeleton

The Implications of Osteocyte Biology for Bone Disease

Conclusions

Acknowledgment

References

Chapter 11. The Regulatory Role of Matrix Proteins in Mineralization of Bone

Introduction

Collagenous Proteins

Intermediate Cartilage Matrix

Osteoadherin, Keratocan, and Lumican

Bone-Enriched Matrix Proteins

Alkaline Phosphatase

Osteonectin

RGD-Containing Glycoproteins

Osteocalcin

Matrix Gla Protein

Periostin

The Mineralization of Bone Matrix

Acknowledgments

References

Part III: Skeletal Hormones and Regulatory Factors

Chapter 12. Parathyroid Hormone and Parathyroid Hormone-Related Protein

Introduction

Synthesis and Secretion of Parathyroid Hormone

Metabolism of Parathyroid Hormone

Bone-Resorbing Action of Parathyroid Hormone

Effects of PTH on Bone Formation

Renal Actions of Parathyroid Hormone

Parathyroid Hormone-Related Protein as a Mediator of Humoral Hypercalcemia of Malignancy

Physiological Roles of Parathyroid Hormone-Related Protein

Mechanism of Action of Parathyroid Hormone and Parathyroid Hormone-Related Protein

Acknowledgments

References

Chapter 13. Vitamin D: Biology, Actions, and Clinical Implications

Introduction

Vitamin D: Synthesis and Metabolism

Pathways of Activation and Inactivation of Vitamin D

Mechanism of 1,25(OH)₂D Action

Nongenomic Actions of Vitamin D

Genetic Disorders

1,25(OH)₂D₃ Analogs

Action of Vitamin D in Classical Target Organs to Regulate Mineral Homeostasis

Actions of 1,25(Oh)₂D in Nonclassical Target Organs

Vitamin D and Osteoporosis

References

Chapter 14. Regulation of Bone Cell Function by Estrogens

Introduction

Estrogen Biosynthesis

Estrogen Receptors

Activities in Bone Attributable to Estrogen Receptor α and/or Estrogen Receptor β

Estrogen Receptor Pharmacology

Summary

References

Chapter 15. Androgens and Skeletal Biology: Basic Mechanisms

Introduction

Androgens and the Role of Androgen Metabolism

Cellular Biology of the Androgen Receptor in the Skeleton

The Consequences of Androgen Action In Bone Cells

The Skeletal Effects of Androgen: Animal Studies

Animal Models of Altered Androgen Responsiveness

The Role of Androgen Receptors Versus Aromatization of Testosterone

Androgen Deficiency and Bone Loss: Similarities Between Animal Models and Humans at a Clinical Level

Summary

References

Chapter 16. Phosphatonins

Introduction

Phosphorus Homeostasis

Phosphatonins

Fibroblast Growth Factor-23

Secreted Frizzled-Related Protein 4

Matrix Extracellular Phosphoglycoprotein (MEPE)

Fibroblast Growth Factor 7

Summary

References

Chapter 17. Skeletal Growth Factors

Introduction

Platelet-Derived Growth Factor

Vascular Endothelial Growth Factor

Fibroblast Growth Factor

Transforming Growth Factor Beta

Bone Morphogenetic Proteins

Insulin-Like Growth Factor

Insulin-Like Growth Factor Binding Proteins

Hepatocyte Growth Factor

Acknowledgments

References

Chapter 18. WNT Signaling in Skeletal Homeostasis and Diseases

Introduction

Wnt Signaling

Wnt Signaling in Skeletal Development, Homeostasis, and Diseases

Wnt Signaling Interacts with Other Pathways in Bone Mass Regulation

Wnt Signaling and Mechanical Loading

Targeting the Wnt Pathway for Therapeutic Intervention

Summary

References

Part IV: Skeletal Structure and Biomechanics

Chapter 19. The Mechanical Behavior of Bone

Introduction

Introduction to Bone Mechanics

Role of Bone Composition and Microstructure on Bone Mechanical Properties

Mechanical Behavior of Whole Bone

Age-Related Changes in Bone Mechanics that Contribute to Fracture

Summary

References

Chapter 20. Cellular and Molecular Mechanotransduction in Bone

Introduction

Bone Mechanotransduction

Forms of Mechanical Stimulation – Tissue Mechanics

Cellular and Pericellular Mechanics

Mechanosensing Mechanisms

Mechanically Activated Intracellular Signaling Pathways

Cell–cell Pathways that are Activated or Mediate Effects of Mechanical Stimuli

Conclusion and Implications for Osteoporosis

References

Chapter 21. Adaptation of Skeletal Structure to Mechanical Loading

Introduction and Background

Diaphyseal Compact Bone

Cancellous Bone

Toward a More Mechanistic Understanding of Functional Adaptation in Bone

Conclusion

References

Chapter 22. Biomechanics of Hip and Vertebral Fractures

Introduction

Biomechanics of Hip Fractures

Biomechanics of Vertebral Fractures

Summary and Clinical Implications

References

Chapter 23. Prevention of Osteoporosis by Physical Signals: Defining a Potential Role for Nondrug Strategies in the Treatment of Musculoskeletal Injury and Disease

Introduction

Bone’s Sensitivity to Mechanical Signals

Structural Demands on the Skeleton

Regulation of Bone Morphology by Physical Signals

Anabolic Potential of Low-magnitude Mechanical Signals

Regulating the Bone Cell Response to Mechanical Signals

Translating Mechanobiology to the Clinic

Summary

Acknowledgments

References

Part V: Epidemiology of Osteoporosis

Chapter 24. Epidemiologic Methods in Studies of Osteoporosis

Introduction

Descriptive and Analytic Studies

Study Designs in Analytical Epidemiologic Studies

Some Useful Epidemiologic Concepts

Frequently Used Statistics

Criteria for Deciding whether an Association Matters

Sample Size Considerations

Measurement Error

Discrepant Results Between Studies Examining Similar Research Questions

Summary

Acknowledgments

References

Chapter 25. Genetic Determinants of Osteoporosis

Introduction

Finding Risk Gene Variants for Complex Traits

Identifying Osteoporosis Risk Gene Variants

Applications and Prospects

References

Chapter 26. Race, Ethnicity, and Osteoporosis

Introduction

Background and Definitions

Ethnoepidemiology of Osteoporosis

Summary

References

Chapter 27. Geographic Variability in Hip and Vertebral Fractures

Introduction

Hip Fractures

Vertebral Fractures

Conclusion

Acknowledgements

References

Chapter 28. Nutrition and Risk for Osteoporosis

Introduction

Problems in the Investigation of Nutritional Effects on Bone

The Notion of A Nutrient Requirement

The Natural Intake of Calcium and Vitamin D

Calcium

Vitamin D

Protein

Vitamin K

Other Essential Nutrients

Conclusion

References

Chapter 29. Physical Activity and Exercise in the Maintenance of the Adult Skeleton and the Prevention of Osteoporotic Fractures

Introduction

The Adult Skeleton and Aging

Theoretical Basis for Physical Activity and Exercise

Physical Activity/Exercise Modes

Exercise and Pharmacological Agents

Exercise and Fracture Rates

Exercise Prescription Recommendations

Conclusions

References

Chapter 30. Premenopausal Reproductive and Hormonal Characteristics and the Risk for Osteoporosis

Introduction

Pregnancy

Age at First Pregnancy

Parity and Nulliparity

Lactation

Ovarian Activity or Menstrual Cycle Characteristics and Bone Mass

Dysfunctional Ovulation

Oral Contraceptive Use

Progestin-Injectable Contraceptives

Oophorectomy

Summary and Implications

References

Chapter 31. Clinical and Epidemiological Studies: Skeletal Changes across Menopause

Introduction

Methodological Issues in Studying Menopause

Pathophysiology of Skeletal Changes at Menopause

Changes in Bone Density across Menopause

Bone Structure/Size Changes

Bone Turnover

Mechanisms Underlying Bone Loss at Menopause

Fracture Risk

Summary

References

Chapter 32. Osteoporosis in Men: Epidemiology, Pathophysiology, and Clinical Characterization

Fractures in Men

The Incidence of Fractures

The Determinants of Fracture

The Major Determinants of Skeletal Health in Men

Age-Related Bone Loss

Causes of Age-Related Bone Loss

Osteoporosis

The Evaluation of Osteoporosis in Men

Acknowledgements

References

Chapter 33. Falls as Risk Factors for Fracture

Introduction

Risk Factors for Falls

Risk Factors for Injurious Falls

Falls Prevention Strategies

Methodologic Approaches to Analyzing Falls

Summary and Implications

References

Chapter 34. Nonskeletal Risk Factors for Osteoporosis and Fractures

Introduction

Physical Characteristics

Anthropometric Variables

Lifestyle Factors

References

Chapter 35. Outcomes Following Osteoporotic Fractures

Introduction

Definition

Risk of Refracture

Risk of Mortality

Fracture Burden

Conclusion

References

Part VI: General Pathophysiology of Osteoporosis

Chapter 36. Skeletal Heterogeneity and the Purposes of Bone Remodeling: Implications for the Understanding of Osteoporosis

Introduction

Skeletal Heterogeneity

The Purposes of Bone Remodeling

Implications for Understanding Osteoporosis

References

Chapter 37. On the Evolution and Contemporary Roles of Bone Remodeling

Introduction

The Basics of Bone Remodeling

Skeletal Involvement in Managing Metabolic Imperatives: Roles and Consequences

Calcium, Remodeling, and Skeletal Structure

An Evolutionary Theory on the Origin of Continuous Bone Remodeling

Bone Remodeling and Reproduction

Lactational and Postmenopausal Bone Loss as Antagonistic Pleiotropies

Bone Remodeling, Skeletal Microcracks, and Fatigue Damage

Effects of Remodeling Inhibition on Bone Strength

The Partnership of Bone Remodeling and Modeling

Summary

References

Chapter 38. Cytokines and the Pathogenesis of Osteoporosis

Introduction

Receptor Activator of Nuclear Factor-Kappab Ligand (RANKL), Receptor Activator of Nuclear Factor-Kappab (RANK) and Osteoprotegerin (OPG)

Macrophage Colony-Stimulating Factor

Additional Colony Stimulating Factors

Interleukin-1

Tumor Necrosis Factor

Additional Tumor Necrosis Factor Superfamily Members

Interleukin-6

Additional Interleukin-6 Family Members

Interleukin-8 and Other Chemokines

Interleukin-10

Interleukin 12

Interleukin 15

Interleukin 17, Interleukin 23, and Interleukin 27

Interleukin 18

Interferons

Additional Cytokines

References

Chapter 39. Animal Models for Osteoporosis

Introduction

Goals of Animal Models for Osteoporosis

Specific Animal Models

Mouse

Evaluation of the Osteopenic Skeleton in Animal Models

Fracture Repair

Summary

References

Chapter 40. Bone and Fat

Introduction

Bone and Fat—Epidemiological Studies

Physiology of Adipose Tissue and Energy Expenditure

Adipocytic and Osteoblastic Differentiation

Hormonal Factors that Regulate Bone and Energy Metabolism

Drug-induced Changes in Bone and Fat

References

Chapter 41. Bone Mineral Acquisition in Utero and During Infancy and Childhood

Introduction

Quantitative Assessment of Bone Health in Infants and Children

Bone Acquisition in Utero

Bone Acquisition in the Preterm Infant

Bone Acquisition in Term Infants and Children

References

Chapter 42. Bone Acquisition in Adolescence

Introduction

Measuring Bone Acquisition

Overview of Bone Accrual During Adolescence

Determinants of Bone Acquisition During Adolescence

Summary and Future Directions

References

Chapter 43. Osteoporosis in Childhood and Adolescence

Introduction

Principles of Bone Development

Definition and Diagnosis of Osteoporosis in Children and Adolescents

Pathogenesis and Treatment of Specific Disorders

Summary and Future Directions

References

Chapter 44. Osteoporosis Associated with Pregnancy

Introduction

Calcium Homeostasis

Osteoporosis Associated With Pregnancy

Osteoporosis Associated with Heparin Therapy During Pregnancy

Osteoporosis Associated with Magnesium Sulfate Therapy During Pregnancy

Paradoxical Bone Mineralization in Twin-To-Twin Transfusion Syndrome

Acknowledgments

References

Chapter 45. Osteoporosis in Premenopausal Women

Introduction

Diagnosis of Osteoporosis in Premenopausal Women

Secondary Causes of Osteoporosis in Premenopausal Women

Treatment Considerations for Premenopausal Women with Low Trauma Fractures And/Or Low BMD

Summary and Conclusions

References

Chapter 46. Estrogen Deficiency, Postmenopausal Osteoporosis, and Age-Related Bone Loss

Introduction

Age- and Sex-Specific Skeletal Changes

Secretion and Metabolism of Sex Steroids

Direct Effects of Sex Steroids on Bone

Indirect Effects of Sex Steroids On Bone

Hormonal Determinants of Skeletal Growth And Maturation

Hormonal Determinants of Age-Related Bone Loss in Women

Hormonal Determinants of Age-Related Bone Loss in Men

The Conundrum of Trabecular Bone Loss in Hormone-Sufficient Young Adults

Other Factors Contributing to Osteoporosis

References

Part VII: Spectrum of Secondary Osteoporosis

Chapter 47. Immobilization Osteoporosis

Introduction

Animal Studies

Cellular and Molecular Mechanisms of Reduced Bone Formation after Unloading

Human Studies

References

Chapter 48. Osteoporosis Associated with Illnesses and Medications

Introduction

Metabolic Disorders

Medications

References

Chapter 49. Glucocorticoid-Induced Osteoporosis

Introduction

Epidemiology of Glucocorticoid-Induced Osteoporosis

Prevention and Treatment

The Pathogenesis and Molecular Basis of Glucocorticoid Action on Bone Metabolism and Development

Other Musculoskeletal Effects of Glucocorticoids

Treatment Options and Fracture Risk Reduction

Management of Glucocorticoid-Induced Osteoporosis in Children

References

Chapter 50. Anticonvulsant-Related Bone Disease

Introduction and Historical Perspective

Epidemiology

Clinical Manifestations

Specific Antiepileptic Drugs

Mechanisms of Action

Treatment

References

Chapter 51. Thyroid Hormone and the Skeleton

Introduction

Thyroid Hormone and Skeletal Growth and Maturation

Thyroid Hormone and Mineral Metabolism

Thyroid Hormone and Skeletal Metabolism

Bone Mass and Fracture Risk in Thyroid Disease

Prevention of Thyroid Hormone-Induced Bone Loss

References

Chapter 52. The Skeletal Actions of Parathyroid Hormone in Primary Hyperparathyroidism and in Osteoporosis

Introduction

Parathyroid Hormone, Primary Hyperparathyroidism, and the Skeleton

Parathyroid Hormone And Osteoporosis

Summary

Acknowledgment

References

Chapter 53. Osteogenesis Imperfecta and Other Defects of Bone Development as Occasional Causes of Adult Osteoporosis

Scope of the Problem

Osteogenesis Imperfecta as a Cause of Adult Osteoporosis

Type I Collagen and Osteogenesis Imperfecta

Clinical Overview of Osteogenesis Imperfecta

Type IV Osteogenesis Imperfecta (Omim 166,220)

Recessive forms of Osteogenesis Imperfecta

Genotype Expression in Osteogenesis Imperfecta

The Pathophysiology of Osteogenesis Imperfecta

Organ Involvement in Osteogenesis Imperfecta

Osteoporosis in the Heritable Disorders of Connective Tissue

References

Chapter 54. HIV and Osteoporosis

Aging and HIV

Etiology of Low Bone Mineral Density in HIV

Other Contributing Factors

Vitamin D Deficiency

Special Populations

Nonskeletal Risk Factors for Fracture

Treatment Considerations

Summary

Reference

Chapter 55. Obesity, Diabetes, and Fractures

Obesity and Fractures

Diabetes Mellitus, Bone Mass, and Fractures

Conclusions

References

Chapter 56. Osteoporosis in Organ Transplant Patients

Skeletal Effects of Immunosuppressive Drugs

Effects of Vitamin D on Immunity and Graft Rejection

Effect of Transplantation on Bone and Mineral Metabolism

Evaluation and Management of Osteoporosis in Patients Awaiting Transplantation

Prevention and Treatment of Transplantation Osteoporosis

Summary and Conclusions

References

Chapter 57. Osteoporosis Associated with Rheumatologic Disorders

Introduction

Rheumatoid Arthritis

Juvenile Idiopathic Arthritis

Seronegative Spondyloarthropathies

Systemic Lupus Erythematosus

Acknowledgments

References

Chapter 58. Osteoporosis Associated with Chronic Kidney Disease

Introduction

Stages Of Chronic Kidney Disease

Epidemiology

Pathophysiology

Skeletal Manifestations Of Chronic Kidney Disease

Extraskeletal Calcifications

Treatment

Hypercalciuria

References

Chapter 59. Oral Bone Loss and Systemic Osteoporosis: Weighing the Risk Benefit Ratio of Treatment

Introduction

Diagnosis

Risk Factors for Intraoral Bone Loss

Patterns of Progression of Oral Bone Loss

Oral Bone Loss and Systemic Osteopenia: are They Related?

Treatment of Oral and Systemic Bone Loss

Bisphosphonates: Risk or Benefit?

References

Part VIII: Cancer and Osteoporosis

Chapter 60. Cancer Treatment-Induced Bone Loss in Patients with Breast Cancer: Pathophysiology and Clinical Perspectives

Introduction

Identifying Fracture Risk in Women With Breast Cancer

Bone Loss in Premenopausal Women Receiving Cancer Treatments

Maintaining Bone Health in Breast Cancer Patients

Disease Modifying Effects of Bone Targeted Treatments

Safety

Conclusions

Acknowledgments

References

Chapter 61. Pathophysiology—Prostate Cancer

Introduction

Normal Bone Physiology

Osteoporosis and Androgen Deprivation Therapy Among Men

Distinction Between Osteoporotic Fractures and Disease-related Fractures

Therapy: Classes of Agents

Clinical Trials With BMD and Fracture End Points

Risk Assessment in Men With Prostate Cancer

Safety of Available Therapies

Conclusions and Recommendations

References

Chapter 62. Mechanisms of Bone Destruction in Myeloma

Introduction

Prevalence and Presentation of Myeloma Bone Disease

The Clinical and Economic Burden of Myeloma Bone Disease

Pathophysiology of Myeloma Bone Disease

Pathogenesis of the Increased Osteoclast Activity in Myeloma

Osteoblast Suppression in Myeloma

Treatment of Myeloma Bone Disease

Conclusions

References

Part IX: Diagnosis and Evaluation

Chapter 63. Evaluation of the Patient at Risk for Osteoporosis

Introduction

Medical History

Physical Exam

Laboratory Studies

Imaging

Invasive Procedures

Treatment Decisions

Conclusions

References

Chapter 64. Imaging of Osteoporosis

Introduction

Principal Radiographic Findings in Osteopenia and Osteoporosis

Diseases Characterized by Generalized Osteopenia

Regional Osteoporosis

References

Chapter 65. Osteoporosis: Who Should be Treated? Who Should be Screened?

Introduction

Who Should be Treated?

FRAX Risk Calculator

Potential Impact of Frax Results

Who Should be Screened for OSTEOPOROSIS—BASED Upon Cost Effectiveness

How Well are Osteoporosis Treatment and Screening Guidelines Followed?

Summary

References

Chapter 66. Clinical Use of Bone Densitometry

Introduction

The Evolution of Bone Densitometry

Dual Energy X-ray Absorptiometry

Other Technologies for the Measurement of Bone Density

The Diagnosis of Osteoporosis Based on the Measurement of Bone Density

Assessing Fracture Risk With Bone Densitometry

FRAX®

DXA-based Vertebral Fracture Assessment

DXA-based Aortic Calcification Assessment

Monitoring Changes in Bone Density After Pharmacologic Treatment

Guidelines for Bone Density Testing

Summary

References

Chapter 67. Biochemical Markers of Bone Turnover in Osteoporosis

Introduction

Biochemical Markers of Bone Formation

Biochemical Markers of Bone Resorption

Analytical and Preanalytical Variability

Clinical Use of Bone Turnover Markers in Postmenopausal Osteoporosis

Bone Turnover Markers in Men

Bone Turnover MARKERS—CLINICAL Studies Versus Clinical Practice

Conclusion: What We Know, What We Need to Know

References

Chapter 68. Fracture Risk Assessment: The Development and Application of FRAX®

Introduction

Development and Construct of FRAX®

Calibration of FRAX®

Performance Characteristics

Reversibility of Risk

Validation

Intervention Thresholds

Interpretation and Limitations of FRAX®

Risk Factors Not Considered in FRAX®

Other Applications of FRAX®

References

Part X: PATIENT MANAGEMENT

Chapter 69. Orthopedic Aspects of Osteoporosis

Orthopedic Aspects of Osteoporosis

Geriatric Fracture Care and Care Treatment Pathways

Osteoporotic Bone and Orthopedic Hardware

Lower Extremity Fractures

Upper Extremity Fractures

Spine and Pelvic Fractures

Osteoporosis and Elective Orthopedic Procedures

Osteoporosis Care in Orthopedic Patients

References

Chapter 70. Falls Prevention Interventions

Epidemiology of Falls and Fall-related Injuries in Older People

Risk Factors of Falls

Fall Risk Screening and Assessment

Fall Prevention Strategies

Summary

References

Chapter 71. Physical Therapy, Physical Modalities, and Exercise Regimens in the Management of Osteoporosis

Introduction

Physical Therapist Practice

Prevention of Fracture

Management of the Patient Following A Vertebral Fracture

Management of the Patient Following A Hip Fracture

Exercise Prescription and Exercise Programs

Conclusion

References

Chapter 72. Calcium in the Treatment of Osteoporosis

Introduction

Cotherapy and Therapy

Bone Remodeling, Osteoporosis, and Calcium

The Critical Role of Protein Intake

Calcium Sources and Amounts

Conclusion

Note

References

Chapter 73. Vitamin D and its Metabolites and Analogs in the Management of Osteoporosis

Introduction

Nomenclature

Vitamin D in the Pathogenesis of Osteoporosis

Animal Models

Postmenopausal Osteoporosis

Other Forms of Osteoporosis

Conclusions

Note

References

Chapter 74. Alternative Therapy through Nutrients and Nutraceuticals

Introduction

Phytoestrogens

Dehydroepiandrosterone

Antioxidants

Bicarbonates

B-Vitamins and Homocysteine

Minerals

Conclusion

References

Part XI: Pharmacotherapeutics

Chapter 75. Design Considerations for Clinical Investigations of Osteoporosis

Background: Inference from Phenomena Subject to Variation

Types of Investigational Designs

Principal Types of Bias with Various Designs

When Controlled Trials and Observational Studies Disagree

Design Alternatives

Design Issues of Special Relevance to Investigation of Bone

Ethics of the Placebo

The Dilemma

Burden of Proof and the Null Hypothesis

References

Chapter 76. Lessons from Bone Histomorphometry on the Mechanisms of Action of Osteoporosis Drugs

Introduction

Anticatabolic Therapies

Anabolic Therapies

References

Chapter 77. Estrogen and Estrogen Analogs for Prevention and Treatment of Osteoporosis

Introduction

Estrogen—The First Osteoporosis Therapy

Estrogen Analogs

Points to Consider

References

Chapter 78. Androgens

Introduction

Androgens

Effects of Testosterone on Bone in Men

Effects of Testosterone on Bone in Women

References

Chapter 79. Calcitonin in Osteoporosis

Introduction

Clinical Pharmacology

Clinical Efficacy in Postmenopausal Osteoporosis

Clinical Efficacy in Other Forms of Osteoporosis

Therapeutic Regimens

Analgesic Effect

Safety

Acknowledgments

References

Chapter 80. Bisphosphonates: Pharmacology and Use in the Treatment of Osteoporosis

Introduction and History

Pharmacokinetics and Pharmacodynamics

Treatment of Postmenopausal Osteoporosis: Efficacy

Bisphosphonate Safety

Bisphosphonate Drug Holidays

Summary

References

Chapter 81. Osteonecrosis of the Jaw and Atypical Femoral Fractures

Introduction

Osteonecrosis of the Jaw

Atypical Femur Fractures

References

Chapter 82. Condition Critical: Compliance and Persistence with Osteoporosis Medications

Introduction

Terminology for Medication-based Behaviors

Compliance and Persistence With Osteoporosis Medications: the Problem

Medication-related Reasons for Noncompliance and Nonpersistence

Compliance and Persistence With Osteoporosis Medications: a Solution(s)?

What Went Wrong? Problems With Recent Interventions

Summary

References

Chapter 83. Denosumab for the Treatment of Osteoporosis

Introduction

Denosumab

Efficacy

Bone Histology and Histomorphometry

Withdrawal of Therapy

Safety and Tolerability

Denosumab in Other Populations

Summary

References

Chapter 84. Strontium Ranelate in the Prevention of Osteoporotic Fractures

Introduction

The Antifracture Efficacy of Strontium Ranelate

The Antifracture Effects of Strontium Ranelate in Specific Populations

Microstructure

Quality of Life and COST-effectiveness

Safety of Strontium Ranelate

Preclinical Studies With Strontium Ranelate

Recent Developments

Conclusion

Conflicts of Interest Statement

References

Chapter 85. Parathyroid Hormone Treatment for Osteoporosis

Introduction

Candidates for Anabolic Therapy

Mode of Action

Postmenopausal Osteoporosis

Parathyroid Hormone (1–84) as Monotherapy

Parathyroid Hormone and Antiresorptive Combination/sequential Therapy

Parathyroid Hormone and Hormone Therapy

Parathyroid Hormone Treatment of MEN

Parathyroid Hormone in Special Populations

Persistence of Effect

Rechallenge With Parathyroid Hormone

Conclusion Regarding Osteoporosis Treatment

Other Possible Clinical Applications for Parathyroid Hormone Treatment

References

Chapter 86. New Approaches to Osteo